Lisa Nodzon: Welcome to this virtual roundtable, Managing Patients With CLL in the COVID Era: The Advanced Practitioner's Role. My name is Lisa Nodzon. I am a nurse practitioner in the Department of Malignant Hematology at Moffitt Cancer Center in Tampa, Florida. Joining me today are my two colleagues, Jackie and Katie.
Jackie Broadway-Duren: Hello everyone. My name is Jackie Broadway-Duren and I am a nurse practitioner in the Department of Leukemia at MD Anderson Cancer Center in Houston, Texas.
Katie Tobin: Hi everyone. My name is Katie Tobin and I'm a clinical pharmacist in Malignant Hematology at Moffitt Cancer Center in Tampa, Florida.
Lisa Nodzon: In our third installment, we will focus on shared decision-making in this unique treatment setting with the backdrop of a real-world case study. Mr W. is a 69-year-old male who was diagnosed with Rai stage III B-cell CLL approximately four years ago. Prognostic factors include deletion 13Q, deletion 17P, and IgHV unmutated, so higher risk features. NGS panel showed mutations in TP53, as well as SF3B1. He presents with diffuse lymphadenopathy, persistent B symptoms as well as high-risk genetic features. At that point in time, he was treated with bendamustine and rituximab for four cycles and achieved a complete remission. Approximately 15 months later, he relapses and was started on ibrutinib 420 mg daily monotherapy for a period of about 18 months before he presents again with gradual disease progression by presenting back to the clinic with some swollen lymph nodes, as well as fatigue and drenching night sweats increasing in frequency.
Labs on presentation show a white blood cell count of 33,000 predominantly with the lymphocytes at 26,000, hemoglobin of 11 gm, as well as an ANC of 2.2. LDH is 335, and beta-2 microglobulin at 5.7. On exam, he's got some palpable lymphadenopathy. He's not bulky, somewhere around 2 cm in the cervical region, as well as in the axillary region. He's got a fantastic performance status of 0. And of course we know his past treatment history included the four cycles of bendamustine/rituximab with a CR for about 18 months. And then based on obviously those higher risk prognostic factors, he relapsed and was placed on the single-agent ibrutinib monotherapy. And then again had progressed. So he received ibrutinib for about a period of about 18 months. Important to note that while he was on ibrutinib, he did experience arthralgia that was managed with dose reduction.
So, Jackie, thinking about a patient like this in terms of shared decision-making, recognizing that he has progressed on ibrutinib, he's got a good performance status, relatively young age. What sort of shared decision-making, knowing that this gentleman requires therapy again, would you incorporate when you're thinking about his next line of therapy?
Jackie Broadway-Duren: Okay, thank you for that question, Lisa. So what we would do is look at the patient's history, consider what he's taken, which would be the BR therapy, consider the fact that this patient was treated with ibrutinib. He did pretty well for a while. However, number one, he progressed, secondly, he could not tolerate the full dose of ibrutinib because of arthralgia. So, at this point, it becomes a matter of presenting. What are your treatment options? Are we going to consider singular agent therapy or are we going to look at other types of therapy. We look at what is the patient's performance status at this point, as well as sitting down, doing decision-making with the patient. What do you want to do? What is it – what is your goal? Do you want a time-limited therapy, which we may consider venetoclax at that point, perhaps even as a single agent and then it would be very important at that point to talk to this patient to see whether or not they've been vaccinated. And if they have not, this will be a good time to get vaccinated before we proceed with further therapy recommendations.
Lisa Nodzon: Yeah, it's definitely important for shared decision-making in our patient population, considering that if we have treatment options available for them, it's fairly important to actively engage them in that decision-making. And, Katie, from a pharmacist perspective, are there certain patient characteristics that may make one treatment more feasible than another when it comes to shared decision-making? And particularly if we're thinking about the BTK inhibitors or BCL-2 inhibitor like venetoclax?
Katie Tobin: Yeah, that's a great question. So looking at our BTK inhibitors, there's a lot of things we have to think about. You have to think about like drug interactions. So both acalabrutinib and ibrutinib are substrates of 3A4, which means it comes with a lot of possible drug interactions. So, it's important to review all the patient's medications with them, including herbals. And this gets missed many times. Ibrutinib and acalabrutinib gets sent to a patient's specialty pharmacy, which is normally a mail order. So, the mail order has no idea what other medications they're on for their other disease states. Now acid suppression's also a concern if you're thinking about acalabrutinib. So if we have a patient that has true GERD, that they actually need a PPI, then I would recommend against that agent. Now looking at our BCL-2 inhibitor of venetoclax, this also is a substrate of 3A4. So it comes with a lot of drug interactions.
So, looking at dose adjustments, that's something we have to think about as well, like looking at the patient's baseline renal and hepatic function. So the BTK inhibitors, there are no true dose adjustments in renal impairment, but it's important to note that they have not been studied in severe renal impairment. Now, ibrutinib does have dose adjustments for hepatic impairment, and acalabrutinib is not recommended in severe hepatic impairment. So keep in mind, these both go through 3A4, so it's all hepatic metabolism. Now, venetoclax again, has not been studied in renal impairment and we probably would shy away from that one, just due to the risk of TLS. And we know all the management we need in that realm. Venetoclax is another hepatic metabolizer, so it's not recommended in severe hepatic impairment.
Lisa Nodzon: Yeah. A lot of safety features go around all these oral oncolytics with our patients now. And I think most importantly, as you pointed out, these drugs are coming from typically a mail order specialty pharmacy. And so the patient's often left to be there in the middle, and their neighborhood pharmacist is not aware or other prescribers perhaps, of the drug that these patients are on. And with some of those strong interactions, some of the very common medications make that list that can exacerbate some of those adverse events. So a lot of education goes into these oral oncolytics with our patients.
So, shared decision-making, as we see is really an integrated and collaborative practice between patients as well as their clinical team. As we can see, there's a very complex interplay of medical information sharing and building of consensus towards that next line of therapy. Objectives to very successful shared decision-making are achieved when patients and their families are fully informed of the treatment options, along with benefit/risk, with evidence showing that more engaged patients does lead to improved psychosocial as well as physical wellbeing and outcomes. But most importantly, a multidisciplinary care model for shared decision-making is really important in terms of our delivery model to provide patients support, as well as symptom and side effect management, along with disease education, all of which would lead to patient care optimization for our patients with CLL.
This brings us to the end of the case. Please see the other segments for further discussion about the management of CLL patients in the COVID era or visit advancedpractitioner.com. Thank you for listening today.
